Dual-functionalized calcium nanocomplexes for transfection of cancerous and stem cells: Low molecular weight polycation-mediated colloidal stability and ATP-mediated endosomal release

Abstract

To overcome colloidal instability of calcium phosphate nanoparticles in gene delivery, colloidally stable and endosomolytic Ca2+-based pDNA nanocomplexes (NCs) were designed by a surface coating of biocompatible polycations (PCs; low molecular weight branched polyethyleneimine [bPEI], protamine sulfate and ε-polylysine) and the addition of natural and endosomolytic ATP, respectively. Without remarkable cytotoxicity and colloidal instability, Ca2+/ATP-pDNA/bPEI1.8 kDa NCs having [bPEI1.8 kDa] = 3.6 μg showed 5.8-fold and 4.4-fold higher transfection efficiencies than bPEI25 kDa/pDNA NCs in HepG2 cells and dental pulp stem cells, respectively. In conclusion, pH-sensitive endosomolytic ATP and Ca2+-based gene complexes could be potentials as effective and safe gene delivery vectors in various cells.